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27 December 2002

Actions of paracetamol on cyclooxygenases in tissue and cell homogenates of mouse and rabbit.

Tomasz A. Swierkosz, Lynne Jordan, Melissa McBride, Kevin McGough, Jean Devlin, Regina M. Botting

Med Sci Monit 2002; 8(12): BR496-503 :: ID: 4820

Abstract

BACKGROUND: Paracetamol is a potent analgesic and antipyretic drug, but has only weak anti-inflammatory activity. Unlike aspirin-like drugs, paracetamol does not damage the stomach mucosa or inhibit the aggregation of platelets. The analgesic action of paracetamol is on the central nervous system. In vitro, paracetamol inhibits cyclooxygenase (COX)-1 and -2 in high concentrations but stimulates in low doses. This study examines the stimulation and inhibition of COX-1 and COX-2 in homogenates of mouse and rabbit tissues and in J774.2 cultured mouse macrophages. MATERIAL/METHODS: Mouse and rabbit tissues were removed, homogenised and treated with different concentrations of paracetamol. Prostaglandins (PGs) E2 and I2 were measured in the homogenates to assess the activity of COX-1. Ex vivo synthesis of PGE2 was measured in tissues after treating rabbits with 100 mg/kg paracetamol. J774.2 cultured mouse macrophages treated with bacterial lipopolysaccharide (LPS) to induce COX-2, were treated with varying concentrations of paracetamol and the PGs produced were measured. RESULTS: Low doses of paracetamol stimulated PG production in J774.2 macrophages and stomach mucosa homogenates, but reduced PG production at high concentrations of paracetamol. This stimulation did not occur when co-factors were added. The order of potency of paracetamol on COX-1 or COX-2 in tissue homogenates was as follows: lungs>spleen>brain>J774.2 cells>stomach mucosa. Paracetamol, 100 mg/kg, inhibited COX-1 in stomach mucosa ex vivo much less effectively than in other tissues. CONCLUSIONS: These data support the hypothesis that paracetamol selectively inhibits a COX enzyme which is different from COX-1 or COX-2 and may be a variant of COX-1.

Keywords: Acetaminophen - pharmacology, Spleen - enzymology

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